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  Diabetic retinopathy (DR) is an impediment of diabetes mellitus, which if not treated early may result in complete loss of vision, even without any preemptive symptoms. DR is caused by high level of glucose in the blood, causing alterations in the microvasculature of retina. However, early screening of diabetic patients through retinal fundus imaging, along with proper diagnosis and treatment can control the prevalence of DR complications. Manual inspection of pathological changes in retinal fundus images is an extremely challenging and tedious task. Therefore, computer-aided diagnosis (CAD) system is an efficient and effective method for early detection of DR and can greatly assist the ophthalmologists. CAD system encompasses DR detection and severity grading that includes detection, classification, localization and segmentation of lesions from the fundus images. Significant contributions have been made in DR severity grading using conventional image processing approaches using hand-engineered features and traditional machine-learning (ML) techniques. In the recent years, significant development of deep learning (DL) methods alleviated by the advancement of hardware computation power and efficient learning algorithms, has triumphed over the traditional ML methods in DR detection and grading tasks. Many researchers have employed the established as well as customized DL models in different DR image repositories and reported their findings. In this paper, we conduct a detailed review of the recent state-of-the-art contributions in the field of DL based DR classification by explaining their methodologies and highlighting their advantages and limitations. A detailed comparative study based on certain statistical parameters has also been conducted to quantitatively evaluate the methods, models and preprocessing techniques. In addition, the challenges in designing an efficient, accurate and robust deep-learning model for DR classification are explored in details to help the future research in this field.

We consider a spun-up system of an inner cylinder of fluid surrounded by an outer fluid layer within a rotating cylindrical container, in the absence of gravity. The outer layer may be of differing density and viscosity to the inner layer. If the inner layer is denser than the outer layer then the effect of rotation, in the presence of a perturbation to the interface between the two layers, is to force the inner fluid outwards and the outer fluid inwards, subject to possible surface tension stabilisation. The relative importance of viscosity to rotation is described by an Ekman number. We investigate the behaviour of perturbations to the interface in the inviscid limit and low and high viscosity limits. In the low viscosity limit, perturbations grow as an $O(Ek^{1/2})$ correction to the inviscid growth rate. In the high viscosity limit, perturbations grow as $O(Ek^{-1})$. In the absence of surface tension, the preferred mode of growth is independent of the layer density difference and depends only upon the domain aspect ratio, initial position of the interface, and viscosity contrast. Numerical simulations of the flow are carried out using a volume-of-fluid formulation. The growth rates from these simulations are compared with the theoretical predictions in both low and high viscosity limits and the agreement is seen to be good. Finally, we examine the special case of a single-layer rotating viscous column and describe the preferred-mode boundary between a varicose mode and a spiral mode in the high viscosity, high surface tension limit.

Isotopic analysis of precipitation over the Andaman Island, Bay of Bengal was carried out for the year 2012 and 2013 in order to study the atmospheric controls on rainwater isotopic variations. The oxygen and hydrogen isotopic compositions are typical of the tropical marine sites but show significant variations depending on the ocean-atmosphere conditions; maximum depletion was observed during the tropical cyclones. The isotopic composition of rainwater seems to be controlled by the dynamical nature of the moisture rather than the individual rain events. Precipitation isotopes undergo systematic depletions in response to the organized convection occurring over a large area and are modulated by the integrated effect of convective activities. Precipitation isotopes appear to be linked with the monsoon intraseasonal variability in addition to synoptic scale fluctuations. During the early to mid monsoon the amount effect arose primarily due to rain re-evaporation but in the later phase it was driven by moisture convergence rather than evaporation. Amount effect had distinct characteristics in these two years, which appeared to be modulated by the intraseasonal variability of monsoon. It is shown that the variable nature of amount effect limits our ability to reconstruct the past-monsoon rainfall variability on annual to sub-annual time scale.

Tumor suppressor and upstream master kinase Liver kinase B1 (LKB1) plays a significant role in suppressing cancer growth and metastatic progression. We show that low-LKB1 expression significantly correlates with poor survival outcome in breast cancer. In line with this observation, loss-of-LKB1 rendered breast cancer cells highly migratory and invasive, attaining cancer stem cell-like phenotype. Accordingly, LKB1-null breast cancer cells exhibited an increased ability to form mammospheres and elevated expression of pluripotency-factors (Oct4, Nanog and Sox2), properties also observed in spontaneous tumors in Lkb1 −/− mice. Conversely, LKB1-overexpression in LKB1-null cells abrogated invasion, migration and mammosphere-formation. Honokiol (HNK), a bioactive molecule from Magnolia grandiflora increased LKB1 expression, inhibited individual cell-motility and abrogated the stem-like phenotype of breast cancer cells by reducing the formation of mammosphere, expression of pluripotency-factors and aldehyde dehydrogenase activity. LKB1, and its substrate, AMP-dependent protein kinase (AMPK) are important for HNK-mediated inhibition of pluripotency factors since LKB1-silencing and AMPK-inhibition abrogated, while LKB1-overexpression and AMPK-activation potentiated HNK’s effects. Mechanistic studies showed that HNK inhibited Stat3-phosphorylation/activation in an LKB1-dependent manner, preventing its recruitment to canonical binding-sites in the promoters of Nanog, Oct4 and Sox2. Thus, inhibition of the coactivation-function of Stat3 resulted in suppression of expression of pluripotency factors. Further, we showed that HNK inhibited breast tumorigenesis in mice in an LKB1-dependent manner. Molecular analyses of HNK-treated xenografts corroborated our in vitro mechanistic findings. Collectively, these results present the first in vitro and in vivo evidence to support crosstalk between LKB1, Stat3 and pluripotency factors in breast cancer and effective anticancer modulation of this axis with HNK treatment.

A new mechano-chemical formulation is developed for making flame resistant sisal fibre rope with low chemical loading. Sisal yarn is treated with a different formulation of ammonium sulfamate (AS) (50 g/L and 100 g/L) by following dip-dry approach at room temperature. Limiting oxygen index (LOI) measures the minimum amount of oxygen required in the mixture of nitrogen and oxygen for burning of the sample. Treated sisal showed LOI values of 28–32 and self-extinguishment in vertical flammability test whereas control sisal yarn showed LOI value of 21 and burnt easily within a minute. Forced combustion results revealed that AS treated sisal yarn exhibited 50% lower peak heat release rate (PHRR) than the control sisal yarn. Sisal yarn based rope was prepared by following braiding technique with three single yarns, using different combinations of untreated and treated sisal yarn. Fire retardant sheath yarn is used to cover the untreated sisal yarn present in the core by twisting or braiding. Rope made from sisal yarn has shown LOI value 30–40. Besides, a new method of simultaneous dyeing and flame retardant finishing of sisal rope is also proposed. The physical properties of the ropes were measured and it was found that the extent of strength loss is statistically insignificant at 95% confidence level. The thermal stability of the AS-treated sisal yarn is measured by thermo-gravimetric analysis. Charring behaviour of the control and AS treated sisal fibre was examined using microscopic images and scanning electron microscopy. Besides, in detail mechanism behind flame retardancy is revealed in the context with the help of XRD and FTIR analysis techniques.

Non-Newtonian fluid flow in pipe bends is inevitable in industrial applications. Previous researchers have extensively explored Newtonian flow through curved ducts. However, the non-Newtonian counterpart gets little attention. We study the turbulent flow of shear-dependent fluids obeying the Power-Law model in a pipe manifold containing an in-plane double bend. Ostwald–de Waele's power law is used to model the fluid's rheology. We utilize computational fluid dynamics (CFD) to solve Reynolds-averaged Navier–Stokes (RANS) equations with the k-ε turbulence model. We validate our numerical results with previous experimental results. The in-plane double bend perturbs the flow in the pipe manifold to develop a Prandtl's secondary flow of the first kind. A fully developed flow at the bend upstream is disturbed due to the bend's curvature and regains its fully developed characteristics upon a certain downstream length after the exit of the bend. We study the rheological characteristics of the secondary flow within the bend and the evolution of fluid flow at the bend downstream. We demonstrate that the centrifugal force-dominated secondary flow increases with a decrease of the non-Newtonian power-law index. We capture the camel's-back-shaped velocity profiles within the bend due to accelerating-decelerating flow. The study reveals that the average flow velocity increases along the bend with a corresponding pressure head loss. We quantify this velocity rise by a newly introduced non-dimensional number, viz. enhancement ratio. The double bend's enhancement ratio decreases with an increase in n.

The overexpression of human apurinic/apyrimidinic (AP) endonuclease 1 (APE1/Ref-1), a key enzyme in the DNA base excision repair (BER) pathway, is often associated with tumor cell resistance to various anticancer drugs. In this study, we examined the molecular basis of transcriptional regulatory (nonrepair) function of APE1 in promoting resistance to certain types of drugs. We have recently shown that APE1 stably interacts with Y-box-binding protein 1 (YB-1), and acts as its coactivator for the expression of multidrug resistance gene MDR1 , thereby causing drug resistance. In this study, we show, to the best of our knowledge, for the first time that APE1 is stably associated with the basic transcription factor RNA polymerase II (RNA pol II) and the coactivator p300 on the endogenous MDR1 promoter. The depletion of APE1 significantly reduces YB-1–p300 recruitment to the promoter, resulting in reduced RNA pol II loading. Drug-induced APE1 acetylation, which is mediated by p300, enhances formation of acetylated APE1 (AcAPE1)–YB-1–p300 complex on the MDR1 promoter. Enhanced recruitment of this complex increases MDR1 promoter-dependent luciferase activity and its endogenous expression. Using APE1-downregulated cells and cells overexpressing wild-type APE1 or its nonacetylable mutant, we have demonstrated that the loss of APE1's acetylation impaired MDR1 activation and sensitizes the cells to cisplatin or etoposide. We have thus established the basis for APE1's acetylation-dependent regulatory function in inducing MDR1-mediated drug resistance.

Diffusion MRI (dMRI) in ex vivo human brain specimens is an important research tool for neuroanatomical investigations and the validation of dMRI techniques. Many ex vivo dMRI applications have benefited from very high dMRI resolutions achievable on small-bore preclinical or animal MRI scanners for small tissue samples. However, the investigation of entire human brains post mortem provides the important context of entire white matter (WM) network systems and entire gray matter (GM) areas connected through these systems. The investigation of intact ex vivo human brains in large bore systems creates challenges due to the limited gradient performance and transmit radio-frequency (B1+) inhomogeneities, specially at ultra-high field (UHF, 7T and higher). To overcome these issues, it is necessary to tailor ex vivo diffusion-weighted sequences specifically for high resolution and high diffusion-weighting. Here, we present kT-dSTEAM, which achieves B1+ homogenization across whole human brain specimens using parallel transmit (pTx) on a 9.4T MR system. We use kT-dSTEAM to obtain multi-shell high b-value and high resolution diffusion-weighted data in ex vivo whole human brains. Isotropic whole brain data can be acquired at high b-value (6000–8000 s/mm2) at high resolution (1000 μm) and at moderate b-value (3000 s/mm2) at ultra-high isotropic resolution (400 μm). As an illustration of the advantages of the ultra-high resolution, tractography across the WM/GM border shows less of the unwanted gyral crown bias, and more high-curvature paths connecting the sulcal wall than at lower resolution. The kT-dSTEAM also allows for acquisition of T1 and T2 weighted images suitable for estimating quantitative T1 and T2 maps. Finally, multi-shell analysis of kT-dSTEAM data at variable mixing time (TM) is shown as an approach for ex vivo data analysis which is adapted to the strengths of STEAM diffusion-weighting. Here, we use this gain for multi-orientation modelling and crossing-fiber tractography. We show that multi-shell data allows superior multiple orientation tractography of known crossing fiber structures in the brain stem. •Homogenous T1, T2 and dMRI at 9.4T across ex vivo human brain with kT-dSTEAM.•High b-value (6000–8000 s/mm2) or high resolution (400 μm) dMRI data acquisitions.•Quantitative qT1 and qT2 maps with kT-dSTEAM relaxometry.•Variable TM multi-shell data analysis by incorporating qT1 parameter map.

Background Due to the lack of high-quality evidence which has hindered the development of evidence-based guidelines, there is a need to provide general guidance on cranioplasty (CP) following traumatic brain injury (TBI), as well as identify areas of ongoing uncertainty via a consensus-based approach. Methods The international consensus meeting on post-traumatic CP was held during the International Conference on Recent Advances in Neurotraumatology (ICRAN), in Naples, Italy, in June 2018. This meeting was endorsed by the Neurotrauma Committee of the World Federation of Neurosurgical Societies (WFNS), the NIHR Global Health Research Group on Neurotrauma, and several other neurotrauma organizations. Discussions and voting were organized around 5 pre-specified themes: (1) indications and technique, (2) materials, (3) timing, (4) hydrocephalus, and (5) paediatric CP. Results The participants discussed published evidence on each topic and proposed consensus statements, which were subject to ratification using anonymous real-time voting. Statements required an agreement threshold of more than 70% for inclusion in the final recommendations. Conclusions This document is the first set of practical consensus-based clinical recommendations on post-traumatic CP, focusing on timing, materials, complications, and surgical procedures. Future research directions are also presented.

The knowledge of interaction of a drug with the membrane phospholipids is crucial to decipher its penetration mechanism inside the cell. Tetracycline is a widely used antibiotic effective against various classes of bacteria. In this work, we have employed vibrational sum-frequency generation (VSFG) spectroscopy to understand the molecular-level interaction of tetracycline with a model phospholipid monolayer, 1,2-dipalmitoyl- sn -glycero-3-phosphocholine (DPPC), at the air–water interface. Results suggest that tetracycline molecules are not present on the topmost surface of the water and remain mostly in the bulk aqueous phase. However, due to charge–dipole interaction, the orientation of water molecules in the subphase immediately beneath the topmost layer gets randomized due to its presence. Due to their long hydrophobic aliphatic chains, DPPC molecules are surface active and replace the topmost water layer and increase the polar orientation of interfacial water molecules by generating electric field across the interface. In the presence of the DPPC monolayer, tetracycline molecules get adsorbed from the bulk water to the interface due to electrostatic interactions with the ionic headgroups of DPPC. This interaction also results in the ordering of hydrophobic chains as confirmed by an increase in the VSFG intensity of CH 3 groups of the hydrocarbon chains. We have been successful in unraveling the changes induced in the hydrocarbon backbone of DPPC as a result of such interaction. The water molecules associated with the DPPC monolayer also get randomized in presence of tetracycline molecules. We, for the first time, have studied the dynamics of interfacial water molecules in presence of tetracycline and tetracycline-DPPC environment.